Heavy and prolonged menstrual bleeding

Heavy menstrual bleeding is excessive blood loss during menses that interferes with physical, social, emotional or material quality of life. Objectively it is over 80 mL each cycle, and prolonged bleeding is menses lasting over 8 days. It is the commonest cause of iron deficiency anaemia in premenopausal women. The main clinical point is to assess haemodynamic and iron status, exclude pregnancy, identify structural and bleeding disorder causes, and match treatment to the woman's wish for fertility and contraception.

Physiology. Menstruation follows progesterone withdrawal, with prostaglandin mediated endometrial shedding, vasoconstriction of spiral arterioles, and haemostasis through platelets and coagulation factors.

Classification. The PALM COEIN system: polyp, adenomyosis, leiomyoma, malignancy and hyperplasia; coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not otherwise classified. Structural causes are in the PALM group and non structural in the COEIN group.

Clinical severity. Flooding, clots over 2.5 cm, changing protection every 1 to 2 hours or at night, or a pictorial blood loss assessment chart score over 100 predicts loss over 80 mL.

Temporal patterns. Bleeding since menarche suggests a bleeding disorder. New onset in the late reproductive years suggests fibroids, adenomyosis, polyps or anovulation. Heavy bleeding with intermenstrual bleeding needs endometrial assessment.

History

• Bleeding: duration, flooding, clots, pad or tampon use, nocturnal soiling, cycle length, intermenstrual or postcoital bleeding, and effect on work, sleep and activity.
• Anaemia symptoms: fatigue, dyspnoea, palpitations, headache, pica, restless legs, hair loss.
• Pain: dysmenorrhoea, pelvic pain, dyspareunia (adenomyosis, endometriosis).
• Bleeding disorder screen: heavy periods since menarche, family history, bruising, epistaxis over 10 minutes, bleeding after dental work, surgery or childbirth, postpartum haemorrhage.
• Pregnancy and fertility plans, contraception, cervical screening, sexually transmitted infection risk.
• Drugs: anticoagulants (including apixaban and rivaroxaban), antiplatelet agents, tamoxifen, hormonal therapy, SSRIs, herbal remedies, copper intrauterine device.
• Thyroid, polycystic ovary syndrome, weight change, and systemic disease (liver, kidney).
• Previous treatments and response.

Examination

• Pulse, blood pressure, pallor, BMI, thyroid, hirsutism, bruising.
• Abdomen for masses.
• Speculum: cervix, polyp, lesion, bleeding source.
• Bimanual: uterine size (bulky, boggy in adenomyosis, irregular in fibroids), tenderness, adnexal mass.

Red flags

• Haemodynamic instability, syncope, or haemoglobin under 70 g/L.
• Positive pregnancy test (miscarriage, molar pregnancy, ectopic pregnancy).
• Age over 45 with persistent bleeding, or younger with risk factors (obesity, polycystic ovary syndrome, tamoxifen, Lynch syndrome).
• Intermenstrual or postcoital bleeding, or a visible cervical lesion.
• Pelvic mass or rapidly enlarging uterus.
• Heavy bleeding from menarche or in an adolescent.
• Bleeding on anticoagulants with falling haemoglobin.

Special groups. Adolescents: anovulation is common, but a bleeding disorder is found in a substantial minority and must be tested. Perimenopause: anovulatory cycles, fibroids and hyperplasia. Women on anticoagulants: bleeding is expected; manage with local and hormonal treatment while continuing anticoagulation.

Organised by the PALM COEIN classification.

Structural

• Leiomyoma (submucous, intramural, subserosal): heavy regular periods, bulky uterus.
• Adenomyosis: heavy painful periods, diffusely enlarged tender uterus.
• Endometrial polyp: heavy or intermenstrual bleeding.
• Serious: endometrial hyperplasia, endometrial cancer, uterine sarcoma, cervical cancer.
• Caesarean scar defect, arteriovenous malformation.
• Adnexal tumour producing oestrogen (granulosa cell tumour).

Coagulopathy

• Von Willebrand disease (the commonest inherited disorder in this setting).
• Platelet function disorders, factor VIII or IX deficiency (carriers of haemophilia), factor XI, VII and X deficiency, fibrinogen disorders.
• Immune thrombocytopenia, leukaemia, aplastic anaemia.
• Liver disease, renal failure.
• Anticoagulant and antiplatelet therapy.

Ovulatory dysfunction. Polycystic ovary syndrome, thyroid disease, hyperprolactinaemia, obesity, perimenopause, hypothalamic causes, adolescence.

Endometrial. Chronic endometritis, primary endometrial disorder of haemostasis.

Iatrogenic. Copper intrauterine device, hormonal therapy, tamoxifen, anticoagulants, antiplatelet drugs, SSRIs, antipsychotics.

Pregnancy related and infection. Miscarriage, ectopic pregnancy, molar pregnancy, retained products, pelvic inflammatory disease, cervicitis.

Stepwise reasoning

1. Assess haemodynamic status and exclude pregnancy.
2. Measure haemoglobin and ferritin, and check iron stores.
3. Take a bleeding disorder history and test when it is positive, in adolescents, and when first line treatment fails.
4. Examine for structural disease and image the uterus when examination is abnormal, treatment fails, or symptoms suggest structural disease.
5. Sample the endometrium when indicated.

Tests

• Urine pregnancy test; serum beta hCG when abnormal.
• Full blood count and ferritin. Ferritin under 30 microgram/L indicates iron deficiency; under 100 microgram/L can indicate it with inflammation or chronic disease.
• Thyroid stimulating hormone, and prolactin if oligomenorrhoea or galactorrhoea.
• Coagulation screen: prothrombin time, activated partial thromboplastin time, fibrinogen. Von Willebrand factor antigen, ristocetin cofactor activity and factor VIII for a positive history; levels rise with oestrogen, pregnancy, inflammation and stress, so a normal result in these conditions can be falsely reassuring and testing may need repeating.
• Group and save, and crossmatch for severe bleeding.
• Nucleic acid amplification tests for chlamydia and gonorrhoea when risk is present.
• Cervical screening if due.
• Transvaginal ultrasound: fibroids, adenomyosis, polyps, endometrial thickness, adnexal mass.
• Endometrial biopsy: age 45 or over with persistent heavy bleeding, younger women with risk factors, failed treatment, or thickened endometrium.
• Hysteroscopy with directed biopsy for suspected submucous fibroid, polyp, or persistent bleeding with normal ultrasound.
• MRI pelvis for adenomyosis, fibroid mapping before surgery or embolisation.
• Liver function and renal function when systemic disease is suspected.

Limitations. A bleeding disorder is easily missed with a single test. Ferritin can be falsely normal during inflammation. Pelvic ultrasound can miss small submucous lesions and adenomyosis.

Acute severe bleeding

• Resuscitate: intravenous access, fluids, group and crossmatch, transfuse red cells for haemodynamic instability or symptomatic anaemia.
• Examine and remove clots with speculum; treat a retained product or source.
• Tranexamic acid 1 g intravenously by slow injection (not faster than 1 mL/min) every 8 hours, reduced for renal impairment, or 1 g orally every 6 to 8 hours; maximum 4 g daily; contraindicated with active thromboembolism or subarachnoid haemorrhage.
• Hormonal control (specialist directed): norethisterone 5 mg orally three times daily until bleeding stops, then 5 mg twice daily to complete 3 weeks, or medroxyprogesterone acetate 10 mg orally three times daily for 7 days; a monophasic combined pill (30 to 35 microgram ethinylestradiol) 1 tablet three times daily for up to 7 days then once daily is an alternative when oestrogen is not contraindicated. Antiemetics may be needed with high doses.
• Surgical or procedural: intrauterine Foley balloon tamponade (30 mL), hysteroscopy, uterine curettage, uterine artery embolisation, hysterectomy for refractory bleeding.

Long term treatment (choose by contraception wish, fertility, cause and comorbidity)

• Levonorgestrel 52 mg intrauterine system (first line): reduces blood loss by 70 to 90%, active for 5 years for this indication; irregular spotting for the first 3 to 6 months.
• Tranexamic acid 1 g orally three times daily (up to four times daily) for up to 4 days from the first day of menses; maximum 4 g daily; reduce for renal impairment (serum creatinine 120 to 249 micromol/L, 1 g twice daily; 250 to 500 micromol/L, 1 g once daily; over 500 micromol/L, 500 mg once daily); stop if no benefit after 3 cycles.
• Mefenamic acid 500 mg orally three times daily with food from the first day of bleeding for up to 5 days; maximum 1.5 g daily; avoid in peptic ulcer, renal impairment, and NSAID sensitive asthma. Naproxen 500 mg orally twice daily or ibuprofen 400 mg orally three times daily are alternatives (naproxen maximum 1 g daily, ibuprofen maximum 2.4 g daily).
• Combined oral contraceptive: monophasic pill with 30 to 35 microgram ethinylestradiol, taken cyclically or continuously; contraindicated with migraine with aura, previous thromboembolism, smoking over age 35, uncontrolled hypertension, and some cardiovascular disease.
• Progestogen only: norethisterone 5 mg orally three times daily from day 5 to day 26 of the cycle (cyclical, for anovulatory bleeding), medroxyprogesterone acetate depot 150 mg intramuscularly every 12 weeks, or dienogest (specialist). Expect bleeding changes.
• Gonadotropin releasing hormone analogue: leuprorelin 3.75 mg intramuscularly monthly for up to 3 to 6 months, with add back therapy, to shrink fibroids before surgery; bone density loss.
• Surgical: hysteroscopic polypectomy or myomectomy, endometrial ablation (not in women wanting fertility), uterine artery embolisation, hysterectomy.

Iron deficiency

• Ferrous sulphate 200 mg (65 mg elemental iron) orally once daily or on alternate days; maximum 200 mg three times daily; take on an empty stomach or with vitamin C; constipation, black stools, nausea. Recheck haemoglobin at 2 to 4 weeks (rise of 10 to 20 g/L in 3 weeks), and continue for 3 months after haemoglobin normalises to replace stores.
• Intravenous iron when oral iron is not tolerated, fails or the need is urgent: ferric carboxymaltose 1000 mg (or 15 mg/kg if under 66 kg) as a single infusion over at least 15 minutes, no more than 1000 mg in a single dose and not repeated within a week; check phosphate in prolonged or repeated use (hypophosphataemia).

Bleeding disorders. Tranexamic acid and levonorgestrel intrauterine system with haematology input. Desmopressin 0.3 microgram/kg intravenously (maximum 20 microgram) or intranasal 300 microgram is used for responsive von Willebrand disease, with fluid restriction for 24 hours and sodium monitoring because of hyponatraemia.

Anticoagulated women. Continue anticoagulation unless advised otherwise. Start levonorgestrel intrauterine system or hormonal control with specialist input; tranexamic acid is used with caution.

Monitoring. Review at 3 months with a bleeding chart and haemoglobin and ferritin. Check thyroid stimulating hormone when abnormal. Review long term hormonal therapy yearly.

Referral and escalation. Refer urgently within 2 weeks for suspected cancer. Refer to gynaecology for structural disease, failed first line treatment, and consideration of surgery. Refer to haematology for a suspected bleeding disorder. Refer to an adolescent gynaecology service for heavy bleeding from menarche.

Admission criteria. Haemodynamic instability, haemoglobin under 70 g/L with symptoms, ongoing heavy bleeding needing procedures, pregnancy related bleeding.

Discharge and follow up. Outpatient care for most women. Give clear instructions for treatment timing and iron.

Safety netting. Return for soaking a pad every hour for over 2 hours, dizziness or fainting, chest pain or breathlessness, fever, or unusual pain.